How achievable are COVID-19 clinical trial recruitment targets? A UK observational cohort study and trials registry analysis.
Burge, Sarah W
De Soyza, Anthony
Francis, Darrel P
Knolle, Martin D
McIntyre, Zoe C
Matheson, Nicholas J
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Cunniffe, N. G., Gunter, S. J., Brown, M., Burge, S. W., Coyle, C., De Soyza, A., Dymond, T., et al. (2020). How achievable are COVID-19 clinical trial recruitment targets? A UK observational cohort study and trials registry analysis.. BMJ Open, 10 (10), e044566. https://doi.org/10.1136/bmjopen-2020-044566
OBJECTIVES: To analyse enrolment to interventional trials during the first wave of the COVID-19 pandemic in England and describe the barriers to successful recruitment in the circumstance of a further wave or future pandemics. DESIGN: We analysed registered interventional COVID-19 trial data and concurrently did a prospective observational study of hospitalised patients with COVID-19 who were being assessed for eligibility to one of the RECOVERY, C19-ACS or SIMPLE trials. SETTING: Interventional COVID-19 trial data were analysed from the clinicaltrials.gov and International Standard Randomized Controlled Trial Number databases on 12 July 2020. The patient cohort was taken from five centres in a respiratory National Institute for Health Research network. Population and modelling data were taken from published reports from the UK government and Medical Research Council Biostatistics Unit. PARTICIPANTS: 2082 consecutive admitted patients with laboratory-confirmed SARS-CoV-2 infection from 27 March 2020 were included. MAIN OUTCOME MEASURES: Proportions enrolled, and reasons for exclusion from the aforementioned trials. Comparisons of trial recruitment targets with estimated feasible recruitment numbers. RESULTS: Analysis of trial registration data for COVID-19 treatment studies enrolling in England showed that by 12 July 2020, 29 142 participants were needed. In the observational study, 430 (20.7%) proceeded to randomisation. 82 (3.9%) declined participation, 699 (33.6%) were excluded on clinical grounds, 363 (17.4%) were medically fit for discharge and 153 (7.3%) were receiving palliative care. With 111 037 people hospitalised with COVID-19 in England by 12 July 2020, we determine that 22 985 people were potentially suitable for trial enrolment. We estimate a UK hospitalisation rate of 2.38%, and that another 1.25 million infections would be required to meet recruitment targets of ongoing trials. CONCLUSIONS: Feasible recruitment rates, study design and proliferation of trials can limit the number, and size, that will successfully complete recruitment. We consider that fewer, more appropriately designed trials, prioritising cooperation between centres would maximise productivity in a further wave.
Humans, Pneumonia, Viral, Coronavirus Infections, Hospitalization, Registries, Prospective Studies, Biomedical Research, Patient Selection, Middle Aged, Eligibility Determination, Health Services Accessibility, Female, Male, Randomized Controlled Trials as Topic, Pandemics, United Kingdom, Betacoronavirus, COVID-19, SARS-CoV-2
Dr Burge and Prof Stewart declare funding from a Cancer Research UK Major Centre award (C9685/A25117). Dr Coyle declares funding from the British Heart Foundation. Dr Gkrania-Klotsas is supported by an NIHR Greenshoots personal Award from the Clinical Research Network. Prof Kanagaratnam declares funding from the Imperial College COVID-19 Research Fund. Dr Knolle declares funding from MRC CARP. Dr Torok declares support from a Clinician Scientist Fellowship (Academy of Medical and the Health Foundation) and the NIHR Cambridge Biomedical Research Centre. Dr Warne receives funding from the National Institute for Health Research Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust. Dr Yates’ salary is funded by The British Society for Rheumatology and Versus Arthritis. Dr Matheson declares funding from MRC (CSF MR/P008801/1) and NHSBT (WPA15-02). Dr Li declares funding from the Medical Research Council programme MRC_MC_UU_00002/10. Dr Villar declares funding from the Medical Research Council (grant number: MC_UU_00002/15). Dr Toshner is funded by the NIHR Cambridge Biomedical Research Centre. This work was enabled by co-operation of the NIHR Respiratory Translational Research Collaboration.
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Medical Research Council (MR/P008801/1)
Cancer Research UK (A25117)
Medical Research Council (G0701652)
External DOI: https://doi.org/10.1136/bmjopen-2020-044566
This record's URL: https://www.repository.cam.ac.uk/handle/1810/310718
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